Mechanism of Chlorpyrifos Induced Chronic Nephrotoxicity
Keywords:Organophosphates, nephrotoxicity, oxidative stress, advanced glycation end-products
INTRODUCTION: Chlorpyrifos is one of the most commonly used organophosphates in agriculture. Report on animal models of chronically exposed chlorpyrifos showed significant histo-structural renal damage. Moreover, evidence of high incidence of diabetes mellitus were observed among agricultural workers exposed to organophosphates. Available evidence linking derangement of glucose metabolism pathway with renal damage in this chronically exposed chlorpyrifos is lacking. The aim of this study was to determine the involvement of advanced glycation end-products formation in the development of nephrotoxicity in animals with chronic subcutaneous exposure to chlorpyrifos. MATERIALS AND METHODS: Eighteen rats were divided into three groups, with six rats in each group. Group 1 served as a control group, while Groups 2 and 3 received subcutaneous 3% dimethyl sulfoxide and 97% volume per volume soy oil as a vehicle or chlorpyrifos, respectively, alternate day for 180 days. Blood samples were taken for biochemical analysis. Kidney tissues were examined for immunohistochemistry and gene expression of pathways related to oxidative stress and advanced glycation end-products. RESULTS: Serum fasting glucose, creatinine, advanced glycation end-products and malondialdehyde levels were significantly increased (p<0.05), whereas paraoxonase-1 level was decreased in chlorpyrifos-treated rats compared with the control groups (p<0.05). The proximal tubular cells and the glomeruli of chlorpyrifos-exposed kidney showed strong malondialdehyde and advanced glycation end-products expression respectively. Gene expression of catalase and glutathione reductase were downregulated in the chlorpyrifos-treated rats. CONCLUSION: Glucose derangement and oxidative stress are the possible mechanisms of organophosphate-induced kidney damage.
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